DOPAMINE TRANSPORTER IMAGING BY PET IN AGING AND DISEASE

已知的是，多巴胺能系统在 正常衰老的过程，并在某些运动中加速 精神错乱。正电子发射断层扫描(PET)代表了一种极好的 无创性测定正常人多巴胺能神经元损失率的方法 由于高度的化学特异性而导致的衰老和运动障碍 可以使用目前可用的放射性示踪剂来实现。我们最近做了 开发IIC-Win 35,428作为成像和定量的示踪配体 通过PET检测多巴胺转运蛋白。IIC-WIN 35,428由无线电合成 11C-亚甲基与合适的DES-甲基前体的反应 当比活度大于1000升/毫米勒时。我们之前已经 证明11C-Win 35428与多巴胺转运体结合是 减少帕金森病(PD)，我们现在建议延长我们的 极轻度帕金森病的研究结果和改善的长期目标 我们对多巴胺系统缺陷的认识和PET的开发 影像方法在帕金森病早期生化鉴定中的应用这个目标是 基于目前使用的神经保护疗法对 延缓帕金森病的进展。早期--可能是临床前的生化 帕金森病患者与正常人及其他疾病患者的区别 进行性核上性瘫痪和特发性震颤等疾病， 将允许比现在更早地建立神经保护治疗 仅凭临床诊断就有可能。 11C-WLN 35,428结合的正常老化和相关减少是一种 这项提议的重点，因为一些运动障碍可能代表 加速观察到的变化，作为正常老化过程的一部分。 而其他PET示踪剂还没有可靠地检测到与年龄相关的 突触前多巴胺能神经元的丢失，11C-Win 35,428具有 有可能达到检测细微变化所需的敏感度 在正常衰老时出现的多巴胺能系统中。澄清年龄- 大脑多巴胺系统的相关变化将对 了解正常衰老是如何导致某些疾病的。为 与多巴胺相互作用的药物的开发和使用 神经元。

The dopaminergic system is known to undergo mild degeneration during the course of normal aging and, at an accelerated rate, in certain movement disorders. Positron emission tomography (PET) represents an excellent method to noninvasively measure the loss of dopaminergic neurons in normal aging and movement disorders due to the high chemically specificity that can be achieved using currently available radiotracers. We have recently developed IIC-WIN 35,428 as a tracer ligand for imaging and quantitation of the dopamine transporter by PET. IIC-WIN 35,428 is radio synthesized by the reaction of 11C-methyliodide with an appropriate des-methyl precursor at a specific activity of greater than 1000 Ci/mmole. We have previously demonstrated that 11C-WIN 35428 binding to the dopamine transporter is reduced in Parkinson disease (PD), and we now propose to extend our results to the study of very mild PD with the long-term goals of improving our understanding the deficits in the dopamine system and developing a PET imaging method for the early biochemical identification of PD. This aim is significant based on the current use of neuroprotective therapy for slowing the progression of PD. The early-possibly pre-clinical biochemical discrimination of PD from normal individuals, and those with other disorders such as progressive supranuclear palsy and essential tremor, would permit earlier institution of neuroprotective therapy than is possible by clinical diagnosis alone. Normal aging and associated reductions in 11C-WLN 35,428 binding is a focus of this proposal since some movement disorders may represent acceleration of the changes observed as part of the normal aging process. Whereas other PET tracers have not reliably detected the age-associated loss of pre-synaptic dopaminergic neurons, 11C-WIN 35,428 has the potential to achieve the sensitivity needed to detect the subtle changes in the dopaminergic system that occur in normal aging. Elucidation of age- associated changes in the brain dopamine system would be significant for understanding how normal aging may predispose to certain diseases and. for the development and use of drugs that interact with dopamine-containing neurons.